Reduction of Central Line-Associated Bloodstream Infections and Line Occlusions in Pediatric Intestinal Failure Patients Receiving Long-Term Parenteral Nutrition Using an Alternative Locking Solution, 4% Tetrasodium Ethylenediaminetetraacetic Acid.

BACKGROUND: Patients with intestinal failure (IF) are dependent on parenteral nutrition (PN), however, they are at risk of central line-associated bloodstream infections (CLABSIs) and line complications. Four-percent tetrasodium ethylenediaminetetraacetic acid (EDTA) solution is an effective nonantibiotic, antimicrobial, antibiofilm, and anticoagulant agent. Our objective was to determine 4% tetrasodium EDTA efficacy in preventing CLABSIs and reducing line occlusions in pediatric IF patients. METHODS: We conducted a retrospective cohort study of patients managed at 2 tertiary Canadian pediatric centers between April 2016 and December 2018 who received 4% tetrasodium EDTA solution under the brand name Kitelock. Data were collected for 12 months pre and post-Kitelock. CLABSIs and alteplase administration were compared using a Wilcoxon matched-pairs signed-rank test. Data were reported as medians and frequencies. RESULTS: Twenty patients were included (10 boys; median age, 83 months [range, 8-232 months]). The rate of CLABSIs before 4% tetrasodium EDTA was 2.7+4 per 1000 catheter days. Patients received 4% tetrasodium EDTA for a median of 365 (278-365) days, with no infections in the 12 months post-therapy (P = .002). Median rates of occlusive episodes for the entire cohort before 4% tetrasodium EDTA were 0 (0-5.0) and 0 (0-2.0) after starting therapy (P = .018). In patients with previous occlusions (n = 9), the median episodes of alteplase use previously was 5.5 (2.7-19.2) compared with 2.7 (0-2.7) (P = .018). CONCLUSIONS: Our preliminary findings suggest 4% tetrasodium EDTA solution is effective in reducing CLABSIs and catheter occlusions in pediatric patients with long-term central-access.

Epigenetic correlates of neonatal contact in humans.

Animal models of early postnatal mother-infant interactions have highlighted the importance of tactile contact for biobehavioral outcomes via the modification of DNA methylation (DNAm). The role of normative variation in contact in early human development has yet to be explored. In an effort to translate the animal work on tactile contact to humans, we applied a naturalistic daily diary strategy to assess the link between maternal contact with infants and epigenetic signatures in children 4-5 years later, with respect to multiple levels of child-level factors, including genetic variation and infant distress. We first investigated DNAm at four candidate genes: the glucocorticoid receptor gene, nuclear receptor subfamily 3, group C, member 1 (NR3C1), µ-opioid receptor M1 (OPRM1) and oxytocin receptor (OXTR; related to the neurobiology of social bonds), and brain-derived neurotrophic factor (BDNF; involved in postnatal plasticity). Although no candidate gene DNAm sites significantly associated with early postnatal contact, when we next examined DNAm across the genome, differentially methylated regions were identified between high and low contact groups. Using a different application of epigenomic information, we also quantified epigenetic age, and report that for infants who received low contact from caregivers, greater infant distress was associated with younger epigenetic age. These results suggested that early postnatal contact has lasting associations with child biology.

Population-based 10-year event-free survival after radical prostatectomy for patients with prostate cancer in British Columbia.

INTRODUCTION: We determined (1) the 10-year survival outcomes after radical treatment of prostate cancer and (2) the 10-year event-free survival following radical prostatectomy (RP) at a population-level in British Columbia (BC), Canada. METHODS: We identified all men with a new diagnosis of prostate cancer in BC between 1999 and 2000. Those treated with RP, external beam radiotherapy (EBRT) or brachytherapy (BT) were identified. Overall survival, and prostate cancer specific survival (PCSS) were calculated from diagnosis using the Kaplan-Meier method. For those men treated with RP, we calculated the 10-year event-free survival (freedom from salvage EBRT or androgen ablation, or death from prostate cancer). Reasons for initiating androgen therapy were unknown and may include symptomatic metastatic disease or asymptomatic biochemical recurrence. An important limitation was the absence of prostate-specific antigen data for staging or follow-up. RESULTS: Among 6028 incident cases, RP was the curative-intent treatment within 1 year in 1360 (22.6%) patients, EBRT in 1367 (22.7%), and BT in 357 (5.9%). The 10-year PCSS was 98% for RP, 95% for EBRT and 98% for BT (log rank p < 0.0001). The 10-year overall survival was 87%. The 10-year event-free survival for those treated with RP was 79% and varied with Gleason grade: 87%, 74%, and 52% for Gleason 2-6, 7, and 8-10, respectively (p < 0.0001). CONCLUSIONS: This population-based study provides outcomes which can inform patient decision-making and provide a benchmark to which other therapies can be compared. Event-free rates for patients treated with RP vary with Gleason score. There is room for improvement in the outcomes of patients with high Gleason score treated with RP.

The need for, and utilization of prostate-bed radiotherapy after radical prostatectomy for patients with prostate cancer in British Columbia.

INTRODUCTION: Three randomized trials have demonstrated that post-radical prostatectomy (RP) radiotherapy decreases biochemical relapse for those with adverse pathology. Our purpose was to describe the incidence of pathologic risk factors for recurrence in a contemporary series of patients treated with RP and to describe the use of post-RP radiotherapy. METHODS: All incident prostate cancers diagnosed between January 2005 and December 2007 were identified from the tumour registry. Cases were then linked to radiotherapy records which included dose and modality (external beam radiotherapy and brachytherapy). The pathology reports in the tumour registry were reviewed for pathologic stage, grade and margin status. RESULTS: We identified 9223 patients with prostate cancer. Overall, 36.3% of patients treated with RP had positive margins, and may have benefited from adjuvant radiotherapy. After RP, 332 (15%) patients had radiotherapy to the prostate bed; of these, only 25 (1.1%) received truly adjuvant radiotherapy (delivered within 6 months with a prostate-specific antigen of <0.2 ng/mL). Of the 2181 patients treated with RP, 270 (12%) were seen by a radiation oncologist within 6 months of RP. Of the 1015 patients (47%) with adverse RP pathology (positive margins, extracapsular extension or seminal vesicle invasion), 230 (23%) were seen by a radiation oncologist within 6 months of RP. CONCLUSION: Not all patients with adverse prostatectomy pathology were seen by a radiation oncologist post-prostatectomy, and very few received adjuvant radiotherapy despite almost half of them having risk factors for relapse.

Spontaneous pregnancy loss mediated by abnormal maternal inflammation in rats is linked to deficient uteroplacental perfusion.

Abnormal maternal inflammation during pregnancy is associated with spontaneous pregnancy loss and intrauterine fetal growth restriction. However, the mechanisms responsible for these pregnancy outcomes are not well understood. In this study, we used a rat model to demonstrate that pregnancy loss resulting from aberrant maternal inflammation is closely linked to deficient placental perfusion. Administration of LPS to pregnant Wistar rats on gestational day 14.5, to induce maternal inflammation, caused fetal loss in a dose-dependent manner 3-4 h later, and surviving fetuses were significantly growth restricted. Pregnancy loss was associated with coagulopathy, structural abnormalities in the uteroplacental vasculature, decreased placental blood flow, and placental and fetal hypoxia within 3 h of LPS administration. This impairment in uteroplacental hemodynamics in LPS-treated rats was linked to increased uterine artery resistance and reduced spiral arteriole flow velocity. Pregnancy loss induced by LPS was prevented by maternal administration of the immunoregulatory cytokine IL-10 or by blocking TNF-α activity after treatment with etanercept (Enbrel). These results indicate that alterations in placental perfusion are responsible for fetal morbidities associated with aberrant maternal inflammation and support a rationale for investigating a potential use of immunomodulatory agents in the prevention of spontaneous pregnancy loss.